Clinical presentation, molecular analysis and follow-up of patients with mut methylmalonic acidemia in Shandong province, China

Han, Bing; Nie, Wei; Sun, Meng; Liu, Yingxia; Cao, Zhiyang

doi:10.1016/j.pedneo.2019.07.004

Cited by 14 publications

(9 citation statements)

References 25 publications

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“…While newborn screening may decrease neonatal mortality, 26 it may not prevent neonatal metabolic decompensation, potentially due to the delay until the newborn screening result is available. Additionally, newborn screening may not improve important outcome parameters, including metabolic stability and cognitive development 23,27‐30 . In countries in which MMA and PA is not part of newborn screening but the method is based on obtaining a full acylcarnitine profile, immediate ‘unblinding’ of the profile in children with suggestive clinical signs and symptoms can avoid significant diagnostic delay.…”

Section: Guidelinesmentioning

confidence: 99%

Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision

Forny

Hörster

Ballhausen³

et al. 2021

J of Inher Metab Disea

169

207

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Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article, we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re‐evaluated, analysed and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well‐informed decisions in the context of MMA and PA patient care.

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Section: Guidelinesmentioning

confidence: 99%

Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision

Forny

Hörster

Ballhausen³

et al. 2021

J of Inher Metab Disea

169

207

View full text Add to dashboard Cite

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“…Eight were missense variants and three were frame-shift variants. Seven of the variants were previously reported 11 , 16 – 20 and four variants, c.2008G>A (p.G670S), c.301_302insTA(p.T101Ifs*80), c.984delC (p.W329Gfs*4), and c.319A>T(p.I107F), were not been previously reported in the HGMD and ClinVar databases (Table 2 , Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia

Zhang

Wang

Shen

et al. 2020

Sci Rep

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Methylmalonic acidemia (MMA)-affected patients may have developmental, hematological, neurological, metabolic, ophthalmological, and dermatological clinically abnormal findings. This study aimed to identify mutations in 13 Chinese MMA cases. We provided genetic counseling, treatment, and prenatal diagnosis for the families with MMA. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was performed and the results were confirmed by gas chromatography and mass spectrometry (GC/MS). Variant screening in probands was performed by targeted next-generation sequencing. Identified variants were confirmed by Sanger sequencing. Of these 13 MMA cases, seven were isolated MMA, and among them, six were caused by variants in MMUT and one was caused by a variant in MCEE . The other six cases were MMA with homocystinuria, which was caused by variants in MMACHC . We found six novel variants in three MMA-causing genes as follows: c.2008G>A, c.301_302insTA, c.984delC, and c.319A>T of MMUT ; c.445T>C of MMACHC ; and c.296T>C of MCEE . We provided prenatal diagnosis for two families with MMA at their next pregnancy, and one family had a healthy newborn. In conclusion, our findings expand the spectrum of genotypes in MMA. Effective genetic counseling is required to allow awareness of the patients’ families that MMA disease is treatable and a good prognosis can be obtained.

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“…Chu et al describes one Hmong patient homozygous for p.A555T and compound heterozygous for CUBN mutations in a study using fibroblasts, suggesting a mut − phenotype and B12 responsiveness [16]. Han et al described two patients, compound heterozygous condition with missense variants in combination with the c.1663G > A, one of which had mild hyperammonemia at presentation [17]. Kang et al also mentioned this mutation, however, without detailed description of the clinical information of the carrying patient [18].…”

Section: Discussionmentioning

confidence: 99%

“…In China, the most common mutations include c.729_730insTT(p.D244Lfs*39), c.1106G > A (p.R369H), c.323G > A (p.R108H), and c.1107dupT (p.T370Yfs*22) [8,14]. The c.1663G > A (p.A555T) mutation in the MMUT gene is relatively rare, which is so far reported only in a few cases [7,[15][16][17][18]. Limited information is available on the clinical and biochemical characteristics of patients carrying this mutation.…”

Section: Introductionmentioning

confidence: 99%

A rare mutation c.1663G > A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients

Liang

Shuai

et al. 2021

Orphanet J Rare Dis

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Background Methylmalonic acidemia is an inherited organic acid metabolic disease. It involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be a rare type, which is seen more frequently in Asian than other populations. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype. Methods Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 compound heterozygous patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant. Results Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Developmental delay or intellectual impairment occurred in 4 patients. 100% of these patients (29/29) were responsive to Vitamin B12 administration. The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients. Conclusion Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.

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Clinical presentation, molecular analysis and follow-up of patients with mut methylmalonic acidemia in Shandong province, China

Cited by 14 publications

References 25 publications

Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision

Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision

Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia

A rare mutation c.1663G > A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients

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